American journal of epidemiology
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Comparative Study
Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects.
A conventional Mendelian randomization analysis assesses the causal effect of a risk factor on an outcome by using genetic variants that are solely associated with the risk factor of interest as instrumental variables. However, in some cases, such as the case of triglyceride level as a risk factor for cardiovascular disease, it may be difficult to find a relevant genetic variant that is not also associated with related risk factors, such as other lipid fractions. Such a variant is known as pleiotropic. ⋯ This "multivariable Mendelian randomization" approach is similar to the simultaneous assessment of several treatments in a factorial randomized trial. In this paper, methods for estimating the causal effects are presented and compared using real and simulated data, and the assumptions necessary for a valid multivariable Mendelian randomization analysis are discussed. Subject to these assumptions, we demonstrate that triglyceride-related pathways have a causal effect on the risk of coronary heart disease independent of the effects of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol.
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Evidence from genetic association studies is accumulating rapidly. Field synopses have recently arisen as an unbiased way of systematically synthesizing this evidence. We performed a systematic review and appraisal of published field synopses in genetic epidemiology and assessed their main findings and methodological characteristics. ⋯ These synopses received more citations (P = 0.01) and needed a larger research team (P = 0.02) than synopses without an online database. Overall, field synopses are becoming a valuable tool for the identification of common genetic variants, especially when researchers follow relevant methodological guidelines. Our work provides a summary of the current status of the field synopses published to date and may help interested readers efficiently identify the online resources containing the relevant genetic evidence.
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Symptoms and illnesses reported by veterans of the 1991 Gulf War era are a cause of potential concern for those military members who have deployed to the Gulf region in support of more recent contingency operations in Iraq and Afghanistan. In the present study, we quantified self-reported symptoms from participants in the Millennium Cohort Study, a prospective study representing all US service branches, including both active duty and Reserve/National Guard components (2001-2008). Self-reported symptoms were uniquely compared with those in a cohort of subjects from the 1991 Gulf War to gain context for the present report. ⋯ The prevalence of self-reported CMI symptoms was compared with that collected in 1997-1999 from a study population of US Seabees from the 1991 Gulf War, as well as from deployed and nondeployed subgroups. Although overall symptom reporting was much less in the Millennium Cohort than in the 1991 Gulf War cohort, a higher prevalence of reported CMI was noted among deployed compared with nondeployed contemporary cohort members. An increased understanding of coping skills and resilience and development of well-designed screening instruments, along with appropriate clinical and psychological follow-up for returning veterans, might help to focus resources on early identification of potential long-term chronic disease manifestations.
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The International Agency for Research on Cancer recently classified outdoor air pollution and airborne particulate matter as carcinogenic to humans. However, there are gaps in the epidemiologic literature, including assessment of possible joint effects of cigarette smoking and fine particulate matter (particulate matter less than or equal to 2.5 µm in diameter) on lung cancer risk. ⋯ This suggests small increases in lung cancer risk among persons with both exposures beyond what would be expected from the sum of the effects of the individual exposures alone. Although reductions in cigarette smoking will achieve the greatest impact on lung cancer rates, these results suggest that attempted reductions in lung cancer risk through both tobacco control and air quality management may exceed expectations based on reducing exposure to either risk factor alone.